SGLT2 Inhibitors and Diabetic Ketoacidosis: What You Need to Know About the Hidden Risk

When you hear about SGLT2 inhibitors, you might think of weight loss, better heart health, or kidney protection. And for many people with type 2 diabetes, those benefits are real. But there’s a quiet, dangerous side effect that doesn’t get talked about enough: diabetic ketoacidosis - and not the kind you expect.

What You Don’t Know About DKA Can Kill You

Most people think diabetic ketoacidosis (DKA) means blood sugar over 250 mg/dL, vomiting, fruity breath, and confusion. That’s the classic version. But with SGLT2 inhibitors, the story changes. A growing number of cases show up with blood sugar levels under 200 mg/dL - sometimes even normal. This is called euglycemic DKA, or euDKA. And it’s sneaky.

Because the numbers look okay, patients and even doctors miss it. A 2023 FDA analysis found nearly half of all DKA cases linked to SGLT2 inhibitors had blood glucose below 250 mg/dL. People showed up with nausea, fatigue, abdominal pain, or trouble breathing - symptoms that look like the flu or food poisoning. By the time ketones are checked, it’s already an emergency.

Here’s the hard truth: euDKA isn’t rare. Studies show it happens 2 to 3 times more often with SGLT2 inhibitors than with other diabetes meds like DPP-4 inhibitors. The European Medicines Agency confirmed this in 2023, updating safety labels to warn doctors: “Check for ketoacidosis even if blood sugar isn’t high.”

How SGLT2 Inhibitors Trigger This Risk

SGLT2 inhibitors - like canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin - work by making your kidneys dump sugar into your urine. That lowers blood sugar. But here’s the catch: they also lower insulin slightly and increase glucagon. That pushes your body to burn fat for fuel instead of glucose.

That sounds fine - until you’re sick, fasting, or cutting carbs. Suddenly, your body is flooded with ketones. Normally, insulin would shut that down. But with SGLT2 inhibitors, insulin is already suppressed. And if you’re on low insulin (like if you have type 2 diabetes with beta-cell decline), your body has no brakes.

It’s not just the drug. It’s what happens around it. The biggest triggers? Illness (like a cold or flu), surgery, skipping meals, drinking too much alcohol, or cutting your insulin dose. One study found 33% of euDKA cases happened during illness. Another 24% followed insulin reduction.

Who’s Most at Risk?

Not everyone on SGLT2 inhibitors gets euDKA. But some people are far more vulnerable.

• People with low C-peptide - this means your pancreas isn’t making much insulin anymore. If your C-peptide is below 1.0 ng/mL, your risk jumps to over 2% - compared to less than 1% in those with normal insulin production.
• People with type 1 diabetes - even though these drugs aren’t approved for type 1, some doctors prescribe them off-label. The FDA and ADA warn against this unless under strict supervision.
• Those planning surgery - fasting before surgery can trigger euDKA. Guidelines now say stop SGLT2 inhibitors at least 3 days before any procedure.
• People on high doses - canagliflozin 300 mg carries more risk than 100 mg.
• Those with recent weight loss or low-carb diets - if you’re eating fewer carbs, your body is already primed to burn fat. SGLT2 inhibitors push you over the edge.

One study tracked 1,247 DKA cases linked to these drugs. Over 60% happened within the first year. The average time to onset? Just 28 weeks after starting the pill.

What Doctors Should Do - And What You Should Ask

The American Diabetes Association, the Endocrine Society, and the American Association of Clinical Endocrinologists all agree: education saves lives.

Doctors need to screen before prescribing. Ask: Have you ever had DKA? Do you have signs of insulin deficiency? Are you planning surgery? Are you on a low-carb diet? If any of these are yes, SGLT2 inhibitors might not be the right choice.

And if you’re already on one? You need to know the warning signs: nausea, vomiting, stomach pain, tiredness, trouble breathing, confusion. Don’t wait for high blood sugar. If you feel off - check ketones. Use a urine strip or a blood ketone meter. If ketones are moderate or high, go to the ER. Don’t wait. Don’t try to tough it out.

A 2022 study showed that when patients were taught to check ketones when sick, DKA cases dropped by 67%. That’s not a small win. That’s life-saving.

Why the Debate Still Exists

You might read conflicting studies. Some say SGLT2 inhibitors don’t raise DKA risk. Others say they triple it. What’s going on?

It comes down to who’s being studied. Trials with healthy, insulin-producing type 2 patients show low risk. Real-world data - where people are older, sicker, on less insulin, and eating poorly - shows higher risk. One 2023 meta-analysis of 71,000 people found no difference from placebo. But that was mostly in controlled trials. The real-world data from Canada and the UK, tracking over 350,000 people, showed a 2.85 times higher risk.

And then there’s the type 1 diabetes angle. A 2025 analysis found no increased risk in type 1 patients using SGLT2 inhibitors - but only when insulin was carefully adjusted. That’s not a green light. It’s a warning: only under expert care.

The Bottom Line: Benefits vs. Risk

Let’s be clear: SGLT2 inhibitors work. They cut heart attacks, hospitalizations for heart failure, and kidney decline. In landmark trials like EMPA-REG and DECLARE-TIMI, they saved lives. For many, the benefits outweigh the risk.

But risk isn’t zero. And it’s not evenly distributed. For someone with strong insulin production, no history of DKA, and no planned surgery - the risk is low. For someone with declining beta-cell function, a recent infection, and a low-carb diet? The risk is real. And deadly.

The key isn’t avoiding these drugs altogether. It’s knowing who they’re safe for - and who they’re not. It’s asking the right questions. It’s checking ketones when you’re sick. It’s stopping the pill before surgery. It’s listening to your body when something feels off.

These drugs aren’t magic. They’re powerful tools. And like any tool, they can hurt you if you don’t use them wisely.

What to Do Right Now

If you’re on an SGLT2 inhibitor:

1. Know the symptoms of DKA - nausea, vomiting, stomach pain, fatigue, trouble breathing.
2. Get a ketone test strip or meter. Keep it at home.
3. Check ketones if you’re sick, fasting, or stressed - even if your blood sugar is normal.
4. Stop the drug 3 days before any surgery or medical procedure.
5. Talk to your doctor: Is your insulin production still strong? Are you a good candidate to keep taking this?

If you’re considering starting one:

1. Ask for a C-peptide test. It tells you how much insulin your body still makes.
2. Discuss your diet. Are you cutting carbs? That’s a red flag.
3. Ask: What’s my history with DKA? Have I ever had unexplained nausea or vomiting?
4. Don’t let the weight loss or heart benefits blind you to the hidden danger.